POS0044 EVIDENCE OF A CAUSAL RELATIONSHIP BETWEEN HYPERLIPIDEMIA AND PSORIASIS AND PSORIATIC ARTHRITIS: A MENDELIAN RANDOMIZATION STUDY
Authors: Q. LI, A. Dohey, D. Codner, P. Rahman
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Psoriatic disease (psoriasis and psoriatic arthritis) is a common inflammatory disease associated with obesity. However, recent studies suggest that lipid changes, rather than obesity, may independently drive psoriatic disease [1]. Mendelian randomization (MR) can assess the causal effect of modifiable exposure by measuring the variation of genes of known function. <h3>Objectives</h3> In this study, we perform a two-sample mendelian randomization to investigate the possible causal relationship between polygenic hyperlipidemia and psoriatic disease (psoriasis and psoriatic arthritis). <h3>Methods</h3> The study cohorts (psoriasis, psoriatic arthritis, hyperlipidemia, and controls of European ancestry) were identified from the FinnGen biobank, an academia/industry collaboration aiming to identify genotype-phenotype correlations in the Finnish founder population. Hyperlipidemia was identified by code E4_HYPERLIPNAS, which represents disorders of lipoprotein metabolism and other lipidaemias [2]. The L12_psoriasis code and psoriatic arthritis by M13_PSORIARTH code identified psoriatic arthritis. The control population was selected after excluding E4_MEABOLIA, psoriasis, and psoriatic arthritis when appropriate. Genome-wide association studies (GWAS) and summarized data were extracted from public IEU datasets. The single-nucleotide polymorphisms (SNPs) were used as instrumental variables (IV) to identify the potential causal effect. The SNP selection was performed by considering the genome-wide significance, clumping, linkage disequilibrium, and minor allele frequency. The effect alleles were harmonized for exposures and outcomes. An inverse variance weighted (IVW) model was used to estimate causality for each IV in this two-sample MR study. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for causal estimations. The MR was performed in both directions to explore the possibility of reverse causality. <h3>Results</h3> 4535 patients with hyperlipidemia, 4510 with psoriasis, and 1553 patients with psoriatic arthritis (PsA) were identified from the FinnGenn biobank based on their id as noted above. The control patients ranged from 147,221 to 212,242, depending on the cohort being compared. Genetic instruments comprising 5 SNPs for hyperlipidemia, 16 SNPs for psoriasis and 4 SNPs for PsA were used for this two-sample MR. A significant causal effect was noted in hyperlipidemia and psoriasis (OR 1.26 (95% CI 1.097-1.439; p &lt; 0.00009) and hyperlipidemia and PsA (OR 1.35 (95% CI 1.08-1.68; p=0.007) but no causal effect was noted in the reverse direction with psoriasis leading to hyperlipidemia OR 1.02 (95% CI 0.977-1.07; p=0.31) and PsA leading to hyperlipidemia OR 1.03 (95% CI 0,987 to 1.08; p=0.15). <h3>Conclusion</h3> Our two-sample MR study genetically predicted that hyperlipidemia has a potential causal association with psoriatic disease, which leads to a higher risk of psoriasis and PsA. Further validation and molecular studies are required to understand this relationship. If these results were to be validated, targeted reduction of hyperlipidemia may help modify the expression of psoriatic disease. <h3>References</h3> [1]Snekvik, I., et al. Metabolic syndrome and risk of incident psoriasis: prospective data from the HUNT Study, Norway. Br. J. Dermatol. 2019; 180, 94–99 [2]https://risteys.finngen.fi/endpoints/E4_HYPERLIPNAS <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Quan Li: None declared, Amanda Dohey: None declared, Dianne Codner: None declared, Proton Rahman Speakers bureau: Abbott, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, and Pfizer, Consultant of: Abbott, AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, and Pfizer, Grant/research support from: Janssen and Novartis.